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| ID | Type | Description | Link |
|---|---|---|---|
| U01AA026966 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) | NIH |
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The purpose of this research study is to test the safety, tolerability, and effectiveness of Vitamin C (ascorbic acid) intravenous infusion when used to treat alcoholic hepatitis (inflammation of the liver from heavy alcohol use) and sepsis (life-threatening complication of an infection).
Alcoholic hepatitis is inflammation of the liver due to alcohol consumption. It can cause one or more of the following symptoms such as jaundice (yellow discoloration of the eyes and skin), pain on the right side of the abdomen, and is accompanied by an enlarged liver. Sepsis is a life-threatening complication of an infection. As the body tries to fight an infection it sends chemicals into the bloodstream. These chemicals that are trying to fight the infection can cause inflammation. This inflammation can cause damage to many body systems and make them fail. Patients with alcoholic hepatitis and sepsis have low levels of Vitamin C in the bloodstream. Vitamin C has been shown to reduce inflammation and organ dysfunction in patients with severe infections.
The investigators do not yet know if Vitamin C will be effective in alcoholic hepatitis. Taking Vitamin C by mouth is not effective as a treatment in people with this condition so participants will receive the Vitamin C intravenously (IV). Participants will be randomly assigned to receive either Vitamin C or a placebo given through an IV every six hours for four days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin C infusion (ascorbic acid) | Active Comparator | Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) |
|
| Placebo | Placebo Comparator | Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin C | Drug | 200mg/kg/24hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Model for End Stage Liver Disease (MELD) Score | Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR). | Baseline and 96 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score | A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing) |
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Inclusion Criteria:
Alcoholic Hepatitis diagnosed by one of the following methods:
Suspected or proven infection
Presence of systemic inflammatory response to infection (fever, hypothermia (low temperature), tachycardia (fast heart rate), leukocytosis (high white blood cell count), leukopenia (low white blood cell count), high respiratory (breathing) rate, or need for mechanical ventilation (a machine to assist in breathing).
Presence of organ failure due to the body's response to infection indicated by any of the following:
Absence of drugs present on urine or blood tests that indicate the possibility of liver damage or mental status changes from other causes
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arun J Sanyal, MD | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Vitamin C Infusion (Ascorbic Acid) | Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours |
| FG001 | Placebo | Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Vitamin C Infusion (Ascorbic Acid) | Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Model for End Stage Liver Disease (MELD) Score | Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR). | Labs were not collected from 4 participants on day 4 so change in MELD score could not be calculated for those participants and they are omitted from the analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 96 hours |
|
Up to 90 days after drug infusion
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vitamin C Infusion (Ascorbic Acid) | Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours) Vitamin C: 200mg/kg/24hours Dextrose 5% in water: 50mL intravenously every 6 hours |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Weakness, hospitalization | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Arun J Sanyal, MD | Virginia Commonwealth University | 804-828-4060 | arun.sanyal@vcuhealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 21, 2020 | Feb 9, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 20, 2018 | Jun 3, 2019 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D006519 | Hepatitis, Alcoholic |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008108 | Liver Diseases, Alcoholic |
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| ID | Term |
|---|---|
| D001205 | Ascorbic Acid |
| D005947 | Glucose |
| D014867 | Water |
| ID | Term |
|---|---|
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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Study drug will be double-blind with matching placebo. Vitamin C 200mg/kg/24hours or placebo (Dextrose 5% in water) will be given intravenously every 6 hours for up to 96 hours of treatment.
| Dextrose 5% in water | Drug | 50mL intravenously every 6 hours |
|
|
| Baseline and 96 hours |
| Change in Aspartate Aminotransferase (AST) Level | Standard blood test used to determine the severity and nature of liver problems. | Baseline and 96 hours |
| Change in Alanine Aminotransferase (ALT) Level | Standard blood test used to determine the severity and nature of liver problems. | Baseline and 96 hours |
| Change in Total Bilirubin | Standard blood test used to determine the severity and nature of liver problems. | Baseline and 96 hours |
| Change in Alkaline Phosphatase | Standard blood test used to determine the severity and nature of liver problems. | Baseline and 96 hours |
| Change in Albumin | Standard blood test used to determine the severity and nature of liver problems. | Baseline and 96 hours |
| Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0 | Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure) | up to 96 hours |
| Changes to Corrected QT Interval (QTc) | An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm. | Baseline and 96 hours |
| Changes to Urine pH | Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale. | Baseline and 96 hours |
| Changes to Urine Microscopy | Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones. | Baseline and 96 hours |
| Changes to Level of Medical Care | Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline | up to 168 hours |
| ICU-free Days | The number of days not spent in an intensive care unit (ICU) | Day 28 |
| Number of Deaths Due to Any Cause | Any cause of death that is anticipated or unanticipated | Day 28 |
| Number of Deaths Due to Any Cause | Any cause of death that is anticipated or unanticipated | Day 90 |
| Hospital-free Days | The number of days spent outside of the hospital | Day 90 |
| Withdrawal by Subject |
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| Discharge from hospital |
|
Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours
Dextrose 5% in water: 50mL intravenously every 6 hours
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Placebo |
Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours |
|
|
| Secondary | Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score | A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing) | Data not recorded for all participants | Posted | Mean | Standard Deviation | score on a scale | Baseline and 96 hours |
|
|
|
| Secondary | Change in Aspartate Aminotransferase (AST) Level | Standard blood test used to determine the severity and nature of liver problems. | Posted | Mean | Standard Deviation | IU/L | Baseline and 96 hours |
|
|
|
| Secondary | Change in Alanine Aminotransferase (ALT) Level | Standard blood test used to determine the severity and nature of liver problems. | Posted | Mean | Standard Deviation | IU/L | Baseline and 96 hours |
|
|
|
| Secondary | Change in Total Bilirubin | Standard blood test used to determine the severity and nature of liver problems. | Posted | Mean | Standard Deviation | mg/dL | Baseline and 96 hours |
|
|
|
| Secondary | Change in Alkaline Phosphatase | Standard blood test used to determine the severity and nature of liver problems. | Posted | Mean | Standard Deviation | U/L | Baseline and 96 hours |
|
|
|
| Secondary | Change in Albumin | Standard blood test used to determine the severity and nature of liver problems. | Posted | Mean | Standard Deviation | g/dL | Baseline and 96 hours |
|
|
|
| Secondary | Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0 | Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure) | Posted | Number | Adverse Events | up to 96 hours |
|
|
|
| Secondary | Changes to Corrected QT Interval (QTc) | An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm. | Posted | Mean | Standard Deviation | milliseconds | Baseline and 96 hours |
|
|
|
| Secondary | Changes to Urine pH | Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale. | Posted | Mean | Standard Deviation | units on a scale | Baseline and 96 hours |
|
|
|
| Secondary | Changes to Urine Microscopy | Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones. | Posted | Count of Participants | Participants | Baseline and 96 hours |
|
|
|
| Secondary | Changes to Level of Medical Care | Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline | Posted | Count of Participants | Participants | up to 168 hours |
|
|
|
| Secondary | ICU-free Days | The number of days not spent in an intensive care unit (ICU) | Posted | Mean | Standard Deviation | days | Day 28 |
|
|
|
| Secondary | Number of Deaths Due to Any Cause | Any cause of death that is anticipated or unanticipated | Posted | Number | Deaths | Day 28 |
|
|
|
| Secondary | Number of Deaths Due to Any Cause | Any cause of death that is anticipated or unanticipated | Posted | Number | Deaths | Day 90 |
|
|
|
| Secondary | Hospital-free Days | The number of days spent outside of the hospital | Posted | Mean | Standard Deviation | days | Day 90 |
|
|
|
| 5 |
| 10 |
| 2 |
| 10 |
| 7 |
| 10 |
| EG001 | Placebo | Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours Dextrose 5% in water: 50mL intravenously every 6 hours | 4 | 10 | 0 | 10 | 5 | 10 |
| Acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Bladder spasm | Renal and urinary disorders | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | Non-systematic Assessment |
|
| Electrocardiogram QT corrected interval | Investigations | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypophospahtemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypotension | Cardiac disorders | Non-systematic Assessment |
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| QT interval prolonged | Investigations | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D020751 |
| Alcohol-Induced Disorders |
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006880 |
| Hydroxy Acids |
| D002241 | Carbohydrates |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D006878 | Hydroxides |
| D000468 | Alkalies |
| D007287 | Inorganic Chemicals |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
| Day 4 |
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|